Dr. Li uses molecular genetic approaches in the model organism Caenorhabditis elegans to investigate two questions.  The first question concerns how different neurotransmitters affect the behavior of an organism.  The second question addresses elucidating the function of genes implicated in Alzheimer’s disease.

Ph.D. in Neurobiology, Harvard University, 1985
M.S. in Civil Engineering (Operations Research) Columbia University, 1978
A.B. in Mathematics, Barnard College, Columbia University, 1976

Biology 20600 - Introduction to Genetics

Biology 37800 - Science of Sex and Gender

Biology 38400 - Developmental Neurobiology

Biology 48300/A8300 - Laboratory in Biotechnology
 

My lab uses molecular genetic approaches to address two questions in neurobiology. In our first project, we are interested in how different neurotransmitters affect the behavior of an organism. We are using the nematode Caenorhabditis elegans as our model system and have focused on examining the role of a specific class of neurotransmitter, the neuropeptides. We are interested in the family of FMRFamide-related peptides, which have been implicated in pain modulation in mammals. At least 31 genes encode FMRFamide-related peptides, or FLPs, in C. elegans. To understand the role of the different flp genes, we have begun the task of determining the expression pattern and knocking out each flp gene. Although there is functional overlap between the genes, inactivation of certain flp genes leads to behavioral defects, including defects in movement, reproduction, oxygen response, and fat accumulation. Insights into the role of the flp genes may reveal how neuropeptides are used in mammalian systems as well as in parasitic nematodes, which infect over one billion people worldwide. In a second project, we are using C. elegans as a model to examine genes implicated in neurodegenerative disorders. Mutations in the human APP gene have been linked to familial Alzheimer's Disease. The functions of APP and APP-related genes in humans, however, are unclear. C. elegans contains one APP-related gene, apl-1, which encodes a protein that is highly similar to human APP. apl-1 has an essential function in C. elegans. Loss of apl-1 disrupts several developmental processes, including molting and morphogenesis, and results in larval lethality. Expression of the extracellular domain of APL-1 is sufficient to rescue the apl-1 lethality, suggesting that apl-1 acts non-cell autonomously as a signaling molecule. Overexpression of APL-1 also causes several phenotypes, including an incompletely penetrant lethality, suggesting that levels of APL-1 need to be tightly regulated to ensure the animal’s viability. We are examining the role of apl-1 and identifying the genes that act in the same pathway as apl-1. Although different organisms may use APP and related proteins in different functional contexts, the pathways in which they function and the molecules with which they interact are likely to be conserved. Hence, identification of pathways relevant to APL-1 may provide insights into the roles and cellular pathways of human APP.

Recent publications:

Lynch MJ, Mercado AS, Li C (2023) Indirect modulation by FLP-1 peptides on chemotaxis and dispersal behavior in C. elegans.  MicroPubl Biol 2023 Sep 8:2023:10.17912/micropub.biology.000930.  doi: 10.17912/micropub.biology.000930. eCollection 2023.

Buntschuh I, Raps DA, Joseph I, Reid C, Chait A, Totanes R, Sawh M, Li C (2018) FLP-1 neuropeptides modulate sensory and motor circuits in the nematode Caenorhabditis elegans.  PLoS One, 13(1):e0189320. doi: 10.1371/journal.pone.0189320. eCollection 2018

Javer A, Currie M, Lee CW, Hokanson J, Li K, Martineau CN, Yemini E, Grundy LJ, Li C, Ch'ng Q, Schafer WR, Nollen EAA, Kerr R, Brown AEX (2018) An open source platform for analyzing and sharing worm behavior data.  Nat Methods 15:645-646.

Ewald CY, Marfil V, Li C (2016) Alzheimer-related protein APL-1 modulates lifespan through heterochronic gene regulation in Caenorhabditis elegans.  Aging Cell doi: 10.1111/acel.12509.

Chang Y-J, Burton T, Ha L, Huang Z, Olajubelo A, C Li (2015) Modulation of locomotion and reproduction by FLP neuropeptides in the nematode Caenorhabditis elegans.  PLoS One 10(9):e0135164. doi: 10.1371/journal.pone.0135164.

Kim J, Yeon J, Choi S-K, Huh YH, Fang Z, Park SJ, Kim MO, Ryoo ZY, Kang K, Kweon H-S, Joon WB, Li, C, Kim K (2015) The evolutionarily conserved LIM homeodomain protein LIM-4/LHX6 specifies the terminal identity of a cholingeric and peptidergic C. elegans sensory/inter/motor neuron-type.  PLoS Genetics 11(8): e1005480. doi:10.1371/journal.pgen.1005480.

Li C, Timbers TA, Rose JK, Bozorgmehr T, McEwan A, Rankin CR (2013) The FMRFamide-related neuropeptide FLP-20 is required in the mechanosensory neurons during memory for massed training in C. elegans.  Learning and Memory 20:103-108.

Ewald CY, Raps DA, Li C (2012) APL-1, the Alzheimer’s amyloid precursor protein in Caenorhabditis elegans modulates multiple metabolic pathways throughout development.  Genetics 191:493-507.

Ewald CY, Chen R, Tolen L, Shah V, Gillani A, Nasrin A, Li C (2012) Pan-neuronal expression of APL-1, an APP-related protein, disrupts olfactory, gustatory, and touch plasticity in C. elegans.  J Neurosci 32:10156-10169.

Cha DS, Hollis SE, Datia US, Lee S, Ryu J, Jung HR, Kim E, Kim K, Lee M, Li C, Lee MH (2012) Differential subcellular localization of DNA topoisomerase-1 isoforms and their roles during Caenorhabditis elegans development.  Gene Expression Patterns 12:189-195.

Arimoto M,  Koushika S, Choudhary B, Li C, Matsumoto K, Hisamoto N (2011) The C. elegans JIP3 protein UNC-16 functions as an adaptor to link kinesin-1 with cytoplasmic dynein.  J Neurosc 31:2216-2224.

Hoopes, J.T., X. Liu, X. Xu, B. Demeier, E. Folta-Stognlew, C. Li, and Y. Ha (2010) Structural characterization of the E2 domain of APL-1, a C. elegans homolog of human amyloid precursor protein, and its heparin binding site. J. Biol. Chem. 285:2165-2173.

Seid, M., K. Goode, C. Li, and J. Traniello (2008) Age- and subcaste-related patterns of serotonergic immunoreactivity in the optic lobes of the ant Pheidole dentata. Develop. Neurobiol. 68:1325-1333.

Niwa, R., F. Zhou, C. Li, and F. Slack (2008) The expression of the Alzheimer’s amyloid precursor protein-like gene is regulated by developmental timing using microRNAs and their targets I Caenorhabditis elegans. Dev. Biol. 315:418-425.

Liu, T., K. Kim, C. Li, and M. Barr (2007) FMRFamide-like neuropeptides and mechanosensory touch receptor neurons regulate male sexual turning behavior in Caenorhabditis elegans. J. Neurosci. 27:7174-7182.

Hornsten, A., J. Lieberthal, S. Fadia, R. Malins, L. Ha, X. Xu, I. Daigle, M. Markowitz, G. O’Connor, R. Plasterk, and C. Li. (2007) APL-1, a C. elegans protein related to human Amyloid Precursor Protein, is essential for viability. Proc. Natl. Acad. Sci. USA 104:1971-1976. Selected as an Editors’ Choice Science 315:914 (2007).

Novillo, A., S.-J. Won, C. Li, and I.P. Callard (2005) Changes in nuclear receptor and vitellogenin gene expression in response to steroids and heavy metal in Caenorhabditis elegans. Integr. Comp. Biol. 45:61-71.

Shan, G., K. Kim, C. Li, and W.W. Walthall (2005) Convergent genetic programs regulate similarities and differences between related motor neuron classes in Caenorhabditis elegans. Dev. Biol. 280: 494-503.

Li, C. (2005) The ever expanding neuropeptide gene families in the nematode Caenorhabditis elegans. Parasitology 131:S109-127.

Zhao, J., K.L. Townsend, L.C. Schulz, T.H. Kunz, C. Li, E.P. Widmaier (2004) Leptin receptor expression increases in placenta, but not hypothalamus, during gestation in Mus musculus and Myotis lucifugus. Placenta J. 25:712-722.

Kim, K, and C. Li (2004) Differential expression and regulation of flp neuropeptide genes in C. elegans. J. Comp. Neurol. 475:540-550.

Lints, R., L. Jia, K. Kim, C. Li, and S.W. Emmons (2004) Specification of sensory organ identity by selector genes in C. elegans. Dev. Biol. 269:137-151.

Rogers, C., V. Reale, K.Kim, H. Chatwin, C. Li, P. Evans, and M. de Bono (2003) Inhibition of social feeding in C. elegans by FMRFamide-related peptide activation of the NPR-1 receptor. Nature Neurosci. 6:1178-1185.

Book Chapters & Reviews

Li C, Kim K (2014) Family of FLP peptides in Caenorhabditis elegans and related nematodes.  Front Endocrinol Oct 14;5:150. doi: 10.3389/fendo.2014.00150. eCollection 2014.

Alexander A, Marfil V, Li C (2014) Use of Caenorhabditis elegans as a model to study Alzheimer’s disease and other neurodegenerative disorders. Front Genet Sep 5;5:279. doi: 10.3389/fgene.2014.00279. eCollection 2014.

Ewald CY, Li C (2012) Caenorhabditis elegans as a model organism to study APP function.  Experimental Brain Research 217:397-411.

Ewald CY, Li C (2012) The secreted Alzheimer-related amyloid precursor protein fragment has an essential role in C. elegans.  Prion 6:1-4.

Li, C. and K. Kim (2010) Neuropeptide gene families in Caenorhabditis elegans. In Neuropeptide Systems as Targets for Parasite and Pest Control, http://www.eurekah.com/chapter/3715, in press.

Ewald, C.Y. and C. Li (2010) Understanding the molecular basis of Alzheimer’s disease using a Caenorhabditis elegans model system. Brain Structure & Function 214:263-283.

Li, C. and K. Kim (2008) Neuropeptides in C. elegans. In WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.142.1, http://www.wormbook.org NIHMSID #125541.